The cytogenetics of polar bodies: insights into female meiosis and the diagnosis of aneuploidy
The cytogenetics of polar bodies: insights into female meiosis and the diagnosis of aneuploidy
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DOI：
10.1093/molehr/gar024
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发表时间：
2011-05-01
影响因子：
4
通讯作者：
Wells, Dagan
中科院分区：
文献类型：
--
作者：
Fragouli, Elpida;Alfarawati, Samer;Wells, Dagan
雌性减数分裂包括两次细胞分裂，减数分裂I（MI）和II（MII）以及卵母细胞发育暂时停止的两个不同阶段。在MI的情况下，这种停顿可能会持续四到五十年。这一额外的复杂层将雌性配子发生与雄性配子发生区分开来。影响人类生殖成功的唯一最重要的遗传因素是非整倍体。非整倍体胚胎可能在植入前发育过程中发生永久性停滞，无法植入或自发流产。大多数非整倍性起源于女性减数分裂，并随着母亲年龄的增长而变得越来越常见。为了进一步阐明人类卵母细胞非整倍性的本质，我们利用比较基因组杂交（CGH）对308个第一和第二极体（PB）进行了详细的细胞遗传学分析。这些是从70名生育年龄较大的妇女（平均母亲年龄为40.8岁）产生的受精卵母细胞中活检的。总的卵母细胞异常率为70%，MII异常占主导地位的MI（50%对40.3%的非整倍体率）。整个染色体不分离和不平衡的染色单体预分裂，但后者是占主导地位的MI非整倍性的原因。染色体丢失比染色体获得更频繁发生，尤其是在MI期间。发现所有大小的染色体都参与非整倍性事件，尽管涉及较小染色体的错误更常见。这些数据揭示了每次减数分裂后产生的非整倍性谱，表明受孕时存在的卵母细胞衍生的异常与在已建立的妊娠中观察到的异常不同。同样清楚的是，母亲年龄的增加对女性减数分裂有显著的不利影响，这种影响在MII中最为明显。事实上，我们的数据表明，MII可能比MI更容易受到年龄相关错误的影响。
Female meiosis is comprised by two cell divisions, meiosis I (MI) and II (MII) and two different stages at which the development of the oocyte is temporarily halted. In the case of MI, this pause can potentially last for four to five decades. This added layer of complexity distinguishes female gametogenesis from its male counterpart. The single most important genetic factor impacting human reproductive success is aneuploidy. Aneuploid embryos may undergo permanent arrest during preimplantation development, fail to implant or spontaneously abort. Most aneuploidies originate during female meiosis and become increasingly common with advancing maternal age. To shed further light on the nature of aneuploidy in human oocytes, we utilized comparative genomic hybridization (CGH) to provide a detailed cytogenetic analysis of 308 first and second polar bodies (PBs). These were biopsied from fertilized oocytes, generated by 70 reproductively older women (average maternal age of 40.8 years). The total oocyte abnormality rate was 70%, and MII anomalies predominated over MI (50% aneuploidy rate versus 40.3%). Both whole chromosome non-disjunction and unbalanced chromatid predivision were seen, but the latter was the dominant MI aneuploidy-causing mechanism. Chromosome losses occurred more frequently than chromosome gains, especially during MI. Chromosomes of all sizes were found to participate in aneuploidy events, although errors involving smaller chromosomes were more common. These data reveal the spectrum of aneuploidies arising after each meiotic division, indicating that oocyte-derived abnormalities present at conception differ from those observed in established pregnancies. It is also clear that advancing maternal age had a significant adverse effect on female meiosis, and that this effect is most pronounced in MII. Indeed, our data suggest that MII may be more susceptible to age-related errors than MI.